tbuckley/cabot-search huggingface dataset:
Fine Particulate Matter Metal Composition, Oxidative Potential, and Adverse Birth Outcomes in Los Angeles
Authors: Qi Meng, Jonathan Liu, Jiaqi Shen, Irish Del Rosario, Pascale S.J. Lakey, Manabu Shiraiwa, Jason Su, Scott Weichenthal, Yifang Zhu, Farzan Oroumiyeh, Suzanne E. Paulson, Michael Jerrett, Beate Ritz
Journal: Environmental Health Perspectives (2023)

Although many studies have linked prenatal exposure to PM2.5 to adverse birth outcomes, little is known about the effects of exposure to specific constituents of PM2.5 or mechanisms that contribute to these outcomes.Our objective was to investigate effects of oxidative potential and PM2.5 metal components from non-exhaust traffic emissions, such as brake and tire wear, on the risk of preterm birth (PTB) and term low birth weight (TLBW).For a birth cohort of 285,614 singletons born in Los Angeles County, California, in the period 2017-2019, we estimated speciated PM2.5 exposures modeled from land use regression with cokriging, including brake and tire wear related metals (barium and zinc), black carbon, and three markers of oxidative potential (OP), including modeled reactive oxygen species based on measured iron and copper (ROS), OH formation (OPOH), and dithiothreitol (DTT) loss (OPDTT). Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for PTB and TLBW with speciated PM2.5 exposures and PM2.5 mass as continuous variables scaled by their interquartile range (IQR).For both metals and oxidative potential metrics, we estimated increased risks for PTB (ORs ranging from 1.01 to 1.03) and TLBW (ORs ranging from 1.02 to 1.05) per IQR exposure increment that were robust to adjustment for PM2.5 mass. Associations for PM2.5 mass, black carbon, metal components, and oxidative potential (especially ROS and OPOH) with adverse birth outcomes were stronger in Hispanic, Black, and mixed-race or Native American women.Our results indicate that exposure to PM2.5 metals from brake and tire wear and particle components that contribute to oxidative potential were associated with an increased risk of PTB and TLBW in Los Angeles County, particularly among Hispanic, Black, and mixed-race or Native American women. Thus, reduction of PM2.5 mass only may not be sufficient to protect the most vulnerable pregnant women and children from adverse effects due to traffic source exposures. https://doi.org/10.1289/EHP12196.
177Lu-DOTATATE (Lutathera) Therapy in 68Ga-DOTATATE PET/CT-Negative Liver Metastases of a Neuroendocrine Tumor
Authors: David Ventura, Wolfgang Roll, Hans-Udo Kasper, Kambiz Rahbar, Lars Stegger
Journal: Clinical Nuclear Medicine (2023)

Abstract A 73-year-old man with metastatic pancreatic neuroendocrine tumor was evaluated with 68 Ga-DOTATATE PET/CT for peptide receptor radionuclide therapy. Both PET-positive and negative lesions were seen in the liver, along with extrahepatic metastases. Histopathology was obtained from one of the PET-negative liver lesions to exclude secondary malignancy. Histology confirmed a well-differentiated (G2) metastasis of pNET with high somatostatin receptor expression. We initiated peptide receptor radionuclide therapy with close monitoring of the PET-negative liver metastases. We present a rare case, where posttherapeutic scintigraphy revealed vigorous uptake of 177 Lu-DOTATATE even in the 68 Ga-DOTATATE PET-negative liver metastases. Follow-up PET/CT showed a partial response to therapy.
Exacerbated Zika virus–induced neuropathology and microcephaly in fetuses of dengue-immune nonhuman primates
Authors: Wilfried A. A. Saron, Keerthana Shanmugam, Chi-Ching Tung, Ranjit Kumar Patmanathan, Abhay P. S. Rathore, Danielle E. Anderson, Ashley L. St. John
Journal: Science Translational Medicine (2023)

Zika virus (ZIKV) is a mosquito-borne flavivirus that can vertically transmit from mother to fetus, potentially causing congenital defects, including microcephaly. It is not fully understood why some fetuses experience severe complications after in utero exposure to ZIKV, whereas others do not. Given the antigenic similarity between ZIKV and the closely related virus dengue (DENV) and the potential of DENV-specific antibodies to enhance ZIKV disease severity in mice, we questioned whether maternal DENV immunity could influence fetal outcomes in a nonhuman primate model of ZIKV vertical transmission. We found significantly increased severity of congenital Zika syndrome (CZS) in fetuses of DENV-immune cynomolgus macaques infected with ZIKV in early pregnancy compared with naïve controls, which occurred despite no effect on maternal ZIKV infection or antibody responses. Ultrasound measurements of head circumference and biparietal diameter measurements taken sequentially throughout pregnancy demonstrated CZS in fetuses of DENV-immune pregnant macaques. Furthermore, severe CZS enhanced by DENV immunity was typified by reduced cortical thickness and increased frequency of neuronal death, hemorrhaging, cellular infiltrations, calcifications, and lissencephaly in fetal brains. This study shows that maternal immunity to DENV can worsen ZIKV neurological outcomes in fetal primates, and it provides an animal model of vertical transmission closely approximating human developmental timelines that could be used to investigate severe ZIKV disease outcomes and interventions in fetuses.
The natural history of periodontal disease—Part 2: In populations with access to dental care: The Studies of Health in Pomerania (<scp>SHIP</scp>)
Authors: Thomas Kocher, Peter Meisel, Reiner Biffar, Henry Völzke, Birte Holtfreter
Journal: Periodontology 2000 (2023)

Abstract In this descriptive analysis of the 21‐year follow‐up data from the SHIP‐START cohort and the 7‐year follow‐up data from the SHIP‐TREND cohort, we report the progression of clinical attachment levels ( CAL ), age effects on CAL change, and a detailed description of CAL progression and remission. At baseline, 4307 and 4420 persons participated in SHIP‐START and SHIP‐TREND , respectively. At the final follow‐up, 1181 and 2507 subjects were available for evaluation, respectively. In SHIP‐START and SHIP‐TREND participants, the mean CAL progressed by 0.04 and 0.02 mm/year, respectively. The older the participants were, the lower the average annual change in mean CAL (from 0.043 to 0.031 mm/year); annual tooth loss was 0.11–0.14 teeth/year. When participants were ranked according to their annual change in mean CAL , remission was more frequently observed in older subjects. To correctly understand the data, it is important to realize that selection bias due to dropouts during follow‐up favored younger and more health‐conscious persons. In addition, extraction of severely periodontally compromised teeth during follow‐up biased the progression towards zero. Another explanation for these low CAL progression rates is that most sites had little or no change in CAL; this means that CAL progression was partly offset by CAL remission. Therefore, changes in mean CAL do not adequately describe the temporal course of periodontitis. Older age was not a risk factor for CAL progression in either cohort.
68Ga-PSMA-11 PET/CT Imaging in Brain Gliomas and Its Correlation With Clinicopathological Prognostic Parameters
Authors: Priyanka Verma, Braj Kishore Singh, Manoharan Dwark Sudhan, Rupesh Kumar Singh, Swati D. Bagul, Ashok R. Chandak, Brijesh Kumar Soni, Divya Shelly, Sandip Basu
Journal: Clinical Nuclear Medicine (2023)

Gliomas are the most common primary central nervous system tumors, of which the malignant gliomas account for 60%-75%. The primary and secondary brain malignancies are highly treatment resistant, and their marked angiogenesis attracts interest as a potential therapeutic target. The grade of gliomas, Ki-67 index, and IDH mutation status are among the major prognostic markers in gliomas. Prostate-specific membrane antigen (PSMA) is a zinc-dependent peptidase that is not only expressed in prostate cancer cells but also in the tumor neovasculature. The initial PSMA PET studies in central nervous system tumors using 68 Ga-HBED-CC-PSMA ( 68 Ga-PSMA-11) PET tracer confirmed selective target expression in gliomas of different grades, with higher expression in high-grade glioma compared with low-grade glioma.The aim of the present study was to correlate and compare the 68 Ga-PSMA-11 and 18 F-FDG uptake in brain tumors with their clinicopathological prognostic parameters, so as to study their prognostic implications. In addition, the study also aimed to identify patients who are likely to benefit from potential PSMA-targeted therapies.This ongoing prospective study was approved by the institutional scientific and medical ethics committee. The patients with primary or recurrent glioma lesions on MRI underwent regional brain PET/CT scanning with 68 Ga-PSMA-11 and 18 F-FDG. The final histopathology of the brain lesions (glioma grade), Ki-67 index, and IDH mutation status were compared with SUV max values of the 68 Ga-PSMA-11 and 18 F-FDG PET/CT.A total of 15 patients (13 males and 2 females; age range, 21-73 years; median age, 58 years) were included in this study analysis. Among the 15 patients, 10 were treatment naive and 2 were patients with recurrent glioma. Three patients turned out to be WHO grade I-II, 6 belonged to grade III, and 6 grade IV (glioblastoma multiforme) on final histopathology. The 68 Ga-PSMA-11 PET/CT showed tracer uptake in all high-grade gliomas with good tumor-to-background ratio. It was PSMA nonavid in 2/3 low-grade gliomas, and it showed low-grade uptake in 1/3 patients. PSMA expression (as evaluated by SUV max values) was significantly higher in higher-grade tumors, those with IDH mutation wildtype status, and higher Ki-67 indices. FDG PET SUV max also showed significant correlation with these prognostic parameters.In these preliminary results, PSMA PET appears to be an important tool in the evaluation and prognosis of gliomas. PSMA-directed theranostics can be explored as a personalized approach in gliomas with high PSMA uptake. However, with the limitation of small sample size, larger clinical trials are warranted to draw conclusive evidence regarding the same.
Time to Treat the Climate and Nature Crisis as One Indivisible Global Health Emergency
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
Journal: JAMA Network Open (2023)

Over 200 health journals call on the United Nations, political leaders, and health professionals to recognize that climate change and biodiversity loss are one indivisible crisis and must be tackled together to preserve health and avoid catastrophe.This overall environmental crisis is now so severe
Asymptomatic Penetrating Atherosclerotic Ulcer Findings on 18F-FDG PET/CT
Authors: Vanessa Murad, Claudia Ortega, Kate Hanneman, Jennifer Chung, Ur Metser
Journal: Clinical Nuclear Medicine (2023)

We present a case of an 84-year-old man with a history of smoking, hypertension, and coronary artery disease with an incidental spiculated left apical pulmonary nodule, suspicious for a stage I non-small cell lung cancer. 18 F-FDG PET/CT performed for staging, which confirmed a small metabolically active pulmonary nodule. As an incidental finding, there was focal FDG uptake in the proximal descending aorta corresponding to a partially thrombosed outpouching of the aortic wall, in keeping with a penetrating atherosclerotic ulcer.
Rare Variant in Metallothionein 1E Increases the Risk of Type 2 Diabetes in a Chinese Population
Authors: Xiantong Zou, Mengdie Hu, Xiuting Huang, Lingli Zhou, Meng Li, Jing Chen, Liping Ma, Xueying Gao, Yingying Luo, Xiaoling Cai, Yufeng Li, Xianghai Zhou, Na Li, Yuanping Shi, Xueyao Han, Linong Ji
Journal: Diabetes Care (2023)

OBJECTIVE To uncover novel targets for the treatment of type 2 diabetes (T2D) by investigating rare variants with large effects in monogenic forms of the disease. RESEARCH DESIGN AND METHODS We performed whole-exome sequencing in a family with diabetes. We validated the identified gene using Sanger sequencing in additional families and diabetes- and community-based cohorts. Wild-type and variant gene transgenic mouse models were used to study the gene function. RESULTS Our analysis revealed a rare variant of the metallothionein 1E (MT1E) gene, p.C36Y, in a three-generation family with diabetes. This risk allele was associated with T2D or prediabetes in a community-based cohort. MT1E p.C36 carriers had higher HbA1c levels and greater BMI than those carrying the wild-type allele. Mice with forced expression of MT1E p.C36Y demonstrated increased weight gain, elevated postchallenge serum glucose and liver enzyme levels, and hepatic steatosis, similar to the phenotypes observed in human carriers of MT1E p.C36Y. In contrast, mice with forced expression of MT1E p.C36C displayed reduced weight and lower serum glucose and serum triglyceride levels. Forced expression of wild-type and variant MT1E demonstrated differential expression of genes related to lipid metabolism. CONCLUSIONS Our results suggest that MT1E could be a promising target for drug development, because forced expression of MT1E p.C36C stabilized glucose metabolism and reduced body weight, whereas MT1E p.C36Y expression had the opposite effect. These findings highlight the importance of considering the impact of rare variants in the development of new T2D treatments.
Time to Treat the Climate and Nature Crisis as One Indivisible Global Health Emergency
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
Journal: JAMA Surgery (2023)
A scoping review of artificial intelligence-based methods for diabetes risk prediction
Authors: Farida Mohsen, Hamada R H Al-Absi, Noha A Yousri, Nady El Hajj, Zubair Shah
Journal: npj Digital Medicine (2023)

Abstract The increasing prevalence of type 2 diabetes mellitus (T2DM) and its associated health complications highlight the need to develop predictive models for early diagnosis and intervention. While many artificial intelligence (AI) models for T2DM risk prediction have emerged, a comprehensive review of their advancements and challenges is currently lacking. This scoping review maps out the existing literature on AI-based models for T2DM prediction, adhering to the PRISMA extension for Scoping Reviews guidelines. A systematic search of longitudinal studies was conducted across four databases, including PubMed, Scopus, IEEE-Xplore, and Google Scholar. Forty studies that met our inclusion criteria were reviewed. Classical machine learning (ML) models dominated these studies, with electronic health records (EHR) being the predominant data modality, followed by multi-omics, while medical imaging was the least utilized. Most studies employed unimodal AI models, with only ten adopting multimodal approaches. Both unimodal and multimodal models showed promising results, with the latter being superior. Almost all studies performed internal validation, but only five conducted external validation. Most studies utilized the area under the curve (AUC) for discrimination measures. Notably, only five studies provided insights into the calibration of their models. Half of the studies used interpretability methods to identify key risk predictors revealed by their models. Although a minority highlighted novel risk predictors, the majority reported commonly known ones. Our review provides valuable insights into the current state and limitations of AI-based models for T2DM prediction and highlights the challenges associated with their development and clinical integration.
<i>MICB</i> Genomic Variant is Associated with NKG2D-mediated Acute Lung Injury and Death
Authors: Oscar A. Aguilar, Anita E. Qualls, Maria D. R. Gonzalez-Hinojosa, Sarah Obeidalla, V. Eric Kerchberger, Tasha Tsao, Jonathan P. Singer, Mark R. Looney, Wilfred Raymond, Steven R. Hays, Jeffrey A. Golden, Jasleen Kukreja, Ciara M. Shaver, Lorraine B. Ware, Jason Christie, Joshua M. Diamond, Lewis L. Lanier, John R. Greenland, Daniel R. Calabrese
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Acute lung injury (ALI) carries a high risk of mortality but has no established pharmacologic therapy. We previously found that experimental ALI occurs through natural killer (NK) cell NKG2D receptor activation and that the cognate human ligand, MICB, was associated with ALI after transplantation.
Genetic vulnerability to Crohn’s disease reveals a spatially resolved epithelial restitution program
Authors: Toru Nakata, Chenhao Li, Toufic Mayassi, Helen Lin, Koushik Ghosh, Åsa Segerstolpe, Emma L. Diamond, Paula Herbst, Tommaso Biancalani, Shreya Gaddam, Saurabh Parkar, Ziqing Lu, Alok Jaiswal, Bihua Li, Elizabeth A. Creasey, Ariel Lefkovith, Mark J. Daly, Daniel B. Graham, Ramnik J. Xavier
Journal: Science Translational Medicine (2023)

Effective tissue repair requires coordinated intercellular communication to sense damage, remodel the tissue, and restore function. Here, we dissected the healing response in the intestinal mucosa by mapping intercellular communication at single-cell resolution and integrating with spatial transcriptomics. We demonstrated that a risk variant for Crohn’s disease, hepatocyte growth factor activator (HGFAC) Arg 509 His (R509H), disrupted a damage-sensing pathway connecting the coagulation cascade to growth factors that drive the differentiation of wound-associated epithelial (WAE) cells and production of a localized retinoic acid (RA) gradient to promote fibroblast-mediated tissue remodeling. Specifically, we showed that HGFAC R509H was activated by thrombin protease activity but exhibited impaired proteolytic activation of the growth factor macrophage-stimulating protein (MSP). In Hgfac R509H mice, reduced MSP activation in response to wounding of the colon resulted in impaired WAE cell induction and delayed healing. Through integration of single-cell transcriptomics and spatial transcriptomics, we demonstrated that WAE cells generated RA in a spatially restricted region of the wound site and that mucosal fibroblasts responded to this signal by producing extracellular matrix and growth factors. We further dissected this WAE cell–fibroblast signaling circuit in vitro using a genetically tractable organoid coculture model. Collectively, these studies exploited a genetic perturbation associated with human disease to disrupt a fundamental biological process and then reconstructed a spatially resolved mechanistic model of tissue healing.
Time to Treat the Climate and Nature Crisis as One Indivisible Global Health Emergency
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
Journal: JAMA Psychiatry (2023)
68Ga-FAPI-04 Detected Hepatic Arteriovenous Malformation in a Patient With IgA Nephropathy
Authors: Zeyu Zhang, Xiang Ni, Shiwei Guo, Changjing Zuo, Chao Cheng
Journal: Clinical Nuclear Medicine (2023)

A 51-year-old woman with a history of IgA nephropathy was found to have a mass in the right lobe of the liver by abdominal ultrasound. The PET/CT scan revealed elevated 68 Ga-FAPI-04 uptake in the aforementioned lesion, indicating the potential presence of liver cancer. However, subsequent histopathological analysis confirmed it to be an arteriovenous malformation. This case illustrates that 68 Ga-FAPI-04 uptake can occur in arteriovenous malformation and is a benign cause of 68 Ga-FAPI-04 uptake.
Risk Model–Based Lung Cancer Screening and Racial and Ethnic Disparities in the US
Authors: Eunji Choi, Victoria Y. Ding, Sophia J. Luo, Kevin ten Haaf, Julie T. Wu, Jacqueline V. Aredo, Lynne R. Wilkens, Neal D. Freedman, Leah M. Backhus, Ann N. Leung, Rafael Meza, Natalie S. Lui, Christopher A. Haiman, Sung-Shim Lani Park, Loïc Le Marchand, Joel W. Neal, Iona Cheng, Heather A. Wakelee, Martin C. Tammemägi, Summer S. Han
Journal: JAMA Oncology (2023)

The revised 2021 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening have been shown to reduce disparities in screening eligibility and performance between African American and White individuals vs the 2013 guidelines. However, potential disparities across other racial and ethnic groups in the US remain unknown. Risk model-based screening may reduce racial and ethnic disparities and improve screening performance, but neither validation of key risk prediction models nor their screening performance has been examined by race and ethnicity.
Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)
Authors: Sattva S. Neelapu, Julio C. Chavez, Alison R. Sehgal, Narendranath Epperla, Matthew Ulrickson, Emmanuel Bachy, Pashna N. Munshi, Carla Casulo, David G. Maloney, Sven de Vos, Ran Reshef, Lori A. Leslie, Olalekan O. Oluwole, Ibrahim Yakoub-Agha, Rashmi Khanal, Joseph Rosenblatt, Ronald Korn, Weixin Peng, Christine Lui, Jacob Wulff, Rhine Shen, Soumya Poddar, A. Scott Jung, Harry Miao, Sara Beygi, Caron A. Jacobson
Journal: Blood (2023)

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n = 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336.
PSMA Radioligand Therapy in Prostate Cancer
Authors: Ludmila Santiago Almeida, Elba Cristina Sá de Camargo Etchebehere, Irene García Megías, Adriana K. Calapaquí Terán, Boris Hadaschik, Patrick M. Colletti, Ken Herrmann, Francesco Giammarile, Roberto C. Delgado Bolton
Journal: Clinical Nuclear Medicine (2023)

Abstract Diagnosis and treatment of prostate cancer are complex and very challenging, being a major health care burden. The efficacy of radioligand therapy with prostate-specific membrane antigen agents has been proven beneficial in certain clinical indications. In this review, we describe management of prostate cancer patients according to current guidelines, especially focusing on the available clinical evidence for prostate-specific membrane antigen radioligand therapy.